Ionophore (A23187)-induced efflux of [3H]norepinephrine and endogenous norepinephrine in the rat vas deferens.
The calcium ionophore, A23187, produced a concentration-dependent increase in the release of norepinephrine from nerves in the rat vas deferens. Maximum response to A23187 (10(-6) - 10(-5) M) was delayed in onset, occurring 60-80 min after initiation of continuous superfusion with A23187. In fact. after tissue exposure to A23187 (10(-5) M) for only 5 min with subsequent superfusion in A23187-free buffer, a significant but delayed increase in norepinephrine efflux occurred. The A23187-induced increase in efflux of norepinephrine was not altered when neuronal sodium conductance was blocked with tetrodotoxin (3.1 X 10(-7) M) or when Na+, K+ -stimulated ATPase was blocked with ouabain (10(-4) M). Release of norepinephrine by A23187 was calcium-dependent since A23187-induced efflux of norepinephrine was diminished (approximately 50%), although not abolished, in calcium-free buffer. Thus, one component of A23187 action was calcium independent. A23187 caused an increased efflux of both norepinephrine formed endogenously and [3H]norepinephrine taken up into neuronal stores. However, the effects of A23187, both on rate and maximum amount of release were greater for [3H]norepinephrine than for endogenous norepinephrine. The present studies demonstrate that neurotransmitter efflux can be induced by carboxylic ionophores in a calcium-dependent process, and this approach may prove useful in studies evaluating factors that modulate neurotransmitter release processes.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D014649:Vas Deferens / Q000378:metabolism
D000900:Anti-Bacterial Agents; D014316:Tritium; D000001:Calcimycin; D010042:Ouabain; D002118:Calcium; D009638:Norepinephrine